Multifunctional nanoplatforms application in the transcatheter chemoembolization against hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) has the sixth-highest new incidence and fourth-highest mortality worldwide. Transarterial chemoembolization (TACE) is one of the primary treatment strategies for unresectable HCC. However, the therapeutic effect is still unsatisfactory due to the insufficient distribution of antineoplastic drugs in tumor tissues and the worsened post-embolization tumor microenvironment (TME, e.g., hypoxia and reduced pH). Recently, using nanomaterials as a drug delivery platform for TACE therapy of HCC has been a research hotspot. With the development of nanotechnology, multifunctional nanoplatforms have been developed to embolize the tumor vasculature, creating conditions for improving the distribution and bioavailability of drugs in tumor tissues. Currently, the researchers are focusing on functionalizing nanomaterials to achieve high drug loading efficacy, thorough vascular embolization, tumor targeting, controlled sustained release of drugs, and real-time imaging in the TACE process to facilitate precise embolization and enable therapeutic procedures follow-up imaging of tumor lesions. Herein, we summarized the recent advances and applications of functionalized nanomaterials based on TACE against HCC, believing that developing these functionalized nanoplatforms may be a promising approach for improving the TACE therapeutic effect of HCC.

New Insights on Liver-Directed Therapies in Hepatocellular Carcinoma

“…Nanostructures are <100 nm and can be developed to control delivery of drugs or other therapies. One of the limitations of cTACE is that the mixture of ethiodized oil, a hydrophobic agent, and doxorubicin, a hydrophilic agent, is unstable and can lead to a rapid release of the drug which has less tumoricidal effect [69]. In comparison, nanostructures can be deployed as controlled delivery systems to directly deliver the therapeutic agent to the tumor microenvironment; for example, in the setting of hypoxia or acidosis in which systemic chemotherapy can be ineffective [69].…”

“…One of the limitations of cTACE is that the mixture of ethiodized oil, a hydrophobic agent, and doxorubicin, a hydrophilic agent, is unstable and can lead to a rapid release of the drug which has less tumoricidal effect [69]. In comparison, nanostructures can be deployed as controlled delivery systems to directly deliver the therapeutic agent to the tumor microenvironment; for example, in the setting of hypoxia or acidosis in which systemic chemotherapy can be ineffective [69]. Multiple preclinical trials in animal and cell models are focused on encapsulating chemotherapeutic agents into nanoparticles, with promising results in inhibiting tumor growth [70].…”

Engineering polyvinyl alcohol microspheres with capability for use in photothermal/chemodynamic therapy for enhanced transarterial chemoembolization

“…As nanomedicine continues to advance, an increasing number of multifunctional microspheres, including micelles, liposomes, polymeric nanoparticles, and mesoporous silica nanoparticles, among others, are being developed for the application of combination therapy. 4,11 Recently, Ji and colleagues developed a hyaluronic acid-modified polyvinyl alcohol multifunctional microsphere loaded with doxorubicin and PT-2385, an effective HIF-2a inhibitor, to enhance the efficacy of TACE treatment for hepatocellular carcinoma. 12 Photothermal therapy (PTT) is a recently emerged minimally invasive treatment method, which converts light energy into heat, raising the temperature at the tumor site to reach the tumor ablation temperature and effectively kill cancer cells.…”

Aptamer-functionalized nanomaterials (AFNs) for therapeutic management of hepatocellular carcinoma

“…The swift progress of nanotechnology has ushered nanomaterials with distinctive properties into the realm of biomedicine [ 23 , 24 ], notably garnering attention for their role in HCC management [ 25 – 27 ]. These materials, celebrated for their biocompatibility, biodegradability, stability under load, and advantageous surface area-to-volume ratio, offer novel avenues for boosting aptamer efficacy and presence in biological systems [ 28 – 30 ].…”